E Pluribus Unum,
the motto of the United States, could just as well apply to biofilm-forming
bacteria. Bacterial biofilms are far more resistant than individual bacteria to
the armories of antibiotics we have devised to combat them. Now Tim Holm
Jakobsen and Michael Givskov of the University of Copenhagen, and their many
collaborators have pinpointed a constituent of garlic that attacks a key step
in the development of biofilms, in an effort they hope may offer help in
particular for patients with cystic fibrosis. The research is published in the
May 2012 issue of Antimicrobial Agents
and Chemotherapy.

In earlier work, Givskov and his colleagues showed that
“crude extracts of garlic inhibit the expression of a large number of genes
that are controlled by bacterial quorum sensing [communication among bacterial
cells involved in biofilm development], and that extracts promote a rapid
clearing of pulmonary Pseudomonas
aeruginosa infection in mice,” he says. “These findings encouraged us to
identify and assess the efficacy of the pure active compound.”

That compound turned out to be ajoene, the major constituent
of a multitude of sulfur-containing compounds produced when garlic is crushed,
says Jakobsen. The team then showed in P.
aeruginosa that ajoene inhibits expression of 11 genes that are controlled
by quorum sensing. “These key genes are regarded as crucial for the ability of P. aeruginosa to cause disease,” he
says.

“We also found ajoene to reduce the production of
rhamnolipid, a compound that shields the biofilm bacteria from the white blood
cells that otherwise would destroy bacteria, and that by combining ajoene with
the antibiotic tobramycin, it was possible to kill over 90 percent of bacteria
living in a biofilm,” says Jakobsen.

“Our study is part of a series of comprehensive
investigations of natural compounds targeting bacterial quorum sensing systems,
and it further strengthens previous proof of concept research we conducted on
the potential of compounds which block communication among pathogen cells in
contrast to simply killing bacteria, as conventional antibiotics do,” says
Jakobsen. Such alternative approaches “may postpone or minimize development of
antibiotic resistance,” he adds.

Jakobsen says the garlic project grew out of a major
donation from the German Cystic Fibrosis Association. “In CF patients, P. aeruginosa infection leads to
bronchieciasis, pulmonary fibrosis, respiratory failure, and death,” he says.
“Despite intensive antibiotic traatment, CF patients have a life expectancy of
about 40 years, and the main cause of death in CF patients remains
complications associated with [this infection].” Jakobsen’s team and the German
CF Association have patented the action of ajoene against biofilms, and are
seeking a pharmacutical partner to develop antimicrobial drugs based on ajoene.

Jakobsen notes that garlic has been used medicinally “for
thousands of years.” Garlic not only has antibacterial properties; it has
anti-viral, anti-fungal, and anti-protozoal properties as well, and it has
beneficial effects on the cardiovascular and immune systems, as well, he says.